Substance abuse remains a serious medical, public health, and social problem. The impact on destructive public health and health costs compounded with the negative consequences of drugs abuse poses a significant toll on the economy. Despite significant advancement of research in the field treatment of and care of patients with substance abuse has lagged behind because of limited education and training of clinicians on substance abuse problems. The goal of the special issue is to provide the current status on the mechanisms underlying the increased prevalence of opportunistic infections in the drug abuse population, to identify important areas where further research would be beneficial and to open new avenues of investigation for therapeutic development. We aimed these articles for the benefit of both basic and clinical researchers.