HSI programs prioritize the most vulnerable homeless populations, who have been homeless the longest, have disabilities, and are in greatest need of permanent shelter and services. Under the Department of Housing and Urban Development's (HUD) definition, a chronically homeless individual is "one who has experienced homelessness for a year or longer, or who has experienced at least four episodes of homelessness in the last three years and has a disability."

In 2022, on a single January night, there were 127,768 adults experiencing chronic homelessness in America; two thirds of whom were unsheltered and living on the streets as reported in the 2022 Annual Homeless Assessment Report to Congress. Many chronically homeless people have serious mental illness like schizophrenia, bi-polar and PTSD. Many are veterans with co-occurring mental illness and substance abuse disorders. The combination of challenges faced by those experiencing chronic homelessness includes complex health conditions, poor access to coordinated care services, prolonged time living on the streets, in shelters, and in and out of institutional settings, which leads to worsening health conditions, premature mortality, and represents costs to the public that do not result in a decrease in homelessness.