Picone's coverage of war zones and social issues is internationally prominent, and over a career spanning more than three decades, his photojournalism has encompassed 10 conflicts across three continents, the global HIV/AIDS pandemic and the Nuba peoples of Sudan, Africa,[1] among many other subjects.

[2] His work has been featured in a wide range of international publications including Time, Newsweek, The Sydney Morning Herald (SMH),[3][4] The Age,[5] Liberation, Der Spiegel, L'Express, Granta,[6] Independent (UK) and The Observer.

[2] Picone explained to the VICE publication in 2013 that, in contrast with the stereotypical "adrenaline junkie" and voyeur perceptions of war correspondents, he was actually seeking to challenge himself to see if he could remain headstrong under such arduous conditions after having considered the prospect for a number of years: "I wanted … to see if I would be able to keep my head—literally and metaphorically."

[2][14] The "final catalyst", in Picone's words, was the Laurie Lee book As I Walked Out One Midsummer Morning, a fictional account of a young man who leaves his home in Cotswolds, England, UK, in 1943 and eventually finds himself in the Spanish Civil War.

Also in 1991, Picone managed to clandestinely enter Gaza with the assistance of the Palestine Liberation Organisation (PLO), because he "didn't want to be officially attached to the Israeli Army".

Picone's Angolan work also includes images of the MPLA (Popular Movement for the Liberation of Angola) soldiers, sick children, and ex-soldiers who had been chained to mechanical parts in mental hospitals.

Picone, who was accused of voyeurism, later recalled that he was unsure if the man eventually died, but asserted that he was helpless to prevent the incident, and risked being shot by the soldiers if he attempted to intervene.

In his recounting, Picone's focus is the rural town of Rukara, where "nobody was spared"—the parish church was the scene of many devastated corpses, and mounds of dead bodies were piled up in the nearby woods.

[17] Picone was based in Bangkok at the time of the 2010 Thai political protests that were organised by the United Front for Democracy Against Dictatorship ("Red Shirts"), and his detailed account of two army snipers, who he was physically alongside while they were engaged in conflict, was published in SMH.

[23]The photographer completed two trips to the Nuba Mountains, in 1994 and 1996, and his first entry was facilitated by a commander from the Sudanese People's Liberation Army (SPLA), which was warring with the Khartoum government troops at the time.

Picone was forced to leave the Nuba Mountains in 1994 due to his contraction of malaria; however, his subsequent report to Médicins Sans Frontières (MSF) led to the delivery of emergency medicines to the region.

He encountered violence and drunken behaviour, and was compelled to intervene after one episode wherein a woman named "Nancy" was beaten by a heavily intoxicated male—Picone drove her to an Aboriginal community where alcohol was not allowed, hoping that she would be safe there.

"[11] After his relocation to Southeast Asia in 2000, Picone documented the experiences of the Karen ethnic group, including the Kayan tribe, in relation to the ongoing conflict in Myanmar.

[16][25] In October 2015, Picone published a photographic essay on the Nai Soi village, where Kayan tribespeople have become self-sufficient through the tourism income they earn since fleeing Myanmar.

Visitors who want to see the "long-necks" or "giraffe women" who wear the customary brass neck rings of the hill tribe are charged an entry fee to walk through the village.

The founders hired the now-defunct Valhalla Cinema venue in the inner-city suburb of Glebe, wherein two Kodak carousels that alternated between large-scale projections of vertical and horizontal photojournalism images were set up.

[28] For the 2013 instalment of the event that was held annually for a period after its inception, U.S. photographer James Nachtwey showed his Testimony collection at an outdoor exhibition at Circular Quay, which includes images from El Salvador, Nicaragua, Guatemala, Lebanon and Afghanistan.

[28] A partnership was formed for the first time with the Vivid Sydney festival for the 2013 Reportage event, but a non-negotiable censorship decision from the then-CEO of Destination NSW, the organisational owner of the Vivid brand, resulted in the placement of a considerable burden upon the Reportage festival directors who were forced to rearrange sophisticated technology to ensure that projections that had been planned for the outdoor venues were only seen in indoor settings including the works of international artists like Francesco Zizola.

Walkley Award-winning photojournalist Andrew Quilty used the term "nanny state" in an interview with a Junkee Media writer, clarifying that what upset him most was the implementation of merely an individual's decision.

[33] Around the turn of the 21st century, Picone shot The Shearers collection in the rural NSW area of Australia that he had grown up in, documenting an occupation that had "epitomised the machismo and romanticism of the outback."

"[37] Regarding war correspondence specifically, Picone's attitude was expressed as part of a feature piece in Volume 36 of Australia's Digital Photography magazine in 2014, wherein he said to the interviewer that one's role is not voyeuristic, but it is instead to "give someone a voice who doesn't have one."

He also acknowledged, however, that the "grey area" of conflict zones means that he has approached each case according to its own circumstances, and he concluded with the warning that those who seek to "save the world and help everyone" on every assignment will not achieve their original goal.

[14] In a 2012 interview with a Bond University-thesis student, in which all four of the Reportage Festival founders participated, Picone explained the major danger-related challenges faced by photojournalists of his ilk:

Their latest digital release the X-Pro-2 is "off the graph" in terms of sensor quality, has a small discreet retro style that is easy to run with in a war zone and it doesn't scream out "kill me" for my ostentatious—worth way too much money—DSLR camera.

[14] On his website, Picone states that his long-term, ongoing passion for black-and-white photography and traditional darkroom printing is due to the medium's "capacity for both subtlety and drama."