Permeable skin is susceptible to desiccation and must be kept moist in order to facilitate cutaneous respiration; as a result much of the ecology and behavior of the red-backed salamander is restricted by climatic and microclimatic variables, particularly dryness and temperature.

[9] The skin of red-backed salamanders was found to contain Lysobacter gummosus, an epibiotic bacterium that produces the chemical 2,4-diacetylphloroglucinol and inhibits the growth of certain pathogenic fungi.

[5][6][12][13] An alternate explanation for the uneven geographic distribution of the red-backed and lead-backed P. cinereus color morphs involves phenotypic plasticity responding to developmental temperature.

[14][15] However, more recent research indicates that a plastic response to thermal conditions during development also contributes to color morph determination; in one study, P. cinereus eggs incubated at a higher temperature hatched a greater proportion of lead-backed morphs than eggs incubated at a lower temperature.

[16] Red-backed salamanders are mostly insectivorous, but prey on a wide assortment of other small invertebrates including isopods, millipedes, centipedes, pseudoscorpions, harvestmen, spiders, and gastropods.

[17] Some studies have suggested that the unstriped morph has adapted to be better suited for drier and warmer conditions explaining the differences in diets.

The unstriped salamanders can forage in drier leaf litter, so they do not need to protect their territory to the extent that striped morphs do.

Slowed growth and delayed metamorphosis make juvenile P. cinereus more vulnerable to predators and has serious consequences for population survival.

The duration of surface activity is directly limited by the rate of cutaneous water loss to the environment, which is influenced by environmental variables such as altitude, forest canopy cover, and the amount of recent precipitation.

In spring, Plethodon cinereus are more likely to exist in groups of around 2 to 7 individuals under some object covers such as rocks and wood, than in the other seasons, while the density on the forest floor stays constant.

A study in Blackrock Mountain, Virginia indicates that the mean number of salamanders in each quadrant of 100*100 m varies from 1.6 to 3 in spring compared to 0.8 to 1.8 in summer.

A significant increase in the spatial distribution of P. cinereus from spring to summer is thought to be due to intraspecific interference competition.

[20] This may be a consequence of a higher predation risk experienced in the wild by the lead-backed phase, and may also mean lead-phase salamanders could be more vulnerable in captivity settings.

Plethodon cinereus usually directs aggressive behavior towards conspecific as well as heterospecific, as long as it is thought to be a potential competitor.

[22] It is necessary to have a visual display in order to elicit the threat posture of P. cinereus, and there will be no obvious aggressive behavior toward conspecifics and heterospecifics if only chemical cues exist.

For example, Batrachochytrium dendrobatidis, a fungal pathogen that causes a disease called chytridiomycosis, has led to a rapid decline in amphibian populations worldwide.

As evidence, the skin of P. cinereus harbors bacterial microsymbionts such as Janthinobacterium lividum, whose metabolites can inhibit the growth of pathogens.

It also provides a research pathway for future drug development that uses novel antifungal compounds for the treatment of human pathogens.

[23] Males and females of P. cinereus typically establish separate feeding and/or mating territories underneath rocks and logs.

However, some red-backed salamanders are thought to engage in social monogamy, and may maintain co-defended territories throughout their active periods.

As in many Plethodon species, female red-backed salamanders have the ability to store sperm as spermatophore, and have been evidenced in doing so up to eight months prior to the oviposition period in June and July.

Even if people trained the birds to enhance the avoidance by increasing exposure to red efts (juvenile Notophthalmus viridescens), the frequencies of erythrism is never above 25%.

Due to the slow movement of amphibians, it is estimated that the mortality rate of these animals on roads is as high as 10% of the total population each year.

Amongst different sizes of roads, it is known that the interstate highway leads to increased genetic differentiation of Plethodon cinereus by microsatellite examination.

Narrow paved roads reduce the movement of redback salamanders by approximately 25–75% but do not eliminate the dynamic of the population.

[26] Moreover, salamanders are largely affected by forest management practices thus impacting the food web dynamics and nutrient cycling of the ecosystem they are residing in.

For instance, even-aged timber harvesting practices are documented which show significantly low abundance and species richness of amphibian creatures in the area.