Her research centers on the genetic basis of childhood-onset behavior disorders, such as ADHD,[1] and the cognitive and emotional impact of mindfulness meditation on health and wellbeing.

[7] Smalley joined the faculty at UCLA after she completed post-doctoral fellowships in medical genetics and childhood psychopathology, moving from assistant to full professor until her retirement to emeritus in 2011.

[15] In an article for the Huffington Post, she wrote: "As a scientist, I love the challenge of understanding my mind, from the inside, while learning what science tells us from the outside.

"[16] In 2010, Smalley and Diana Winston, a former Buddhist nun and the director of education at MARC, wrote Fully Present: The Science, Art, and Practice of Mindfulness.

[19] She was the keynote speaker at the UCLA Department of Anthropology commencement ceremony in 2013, and the 2017 Children and Adults with Attention Deficit Hyperactivity Disorder (CHADD) annual conference.

[20][21] Smalley majored in biological anthropology at the University of Michigan, and as an undergraduate became interested in population genetics and human evolution.