The Penn/VA Center was founded in 1971 because of great concern over the number of Vietnam veterans returning home addicted to heroin. At that time little was known about the science of addiction, so our program from the very beginning was designed to gather data about the nature of addiction and measure the effects of available treatments. In other words, the goals were always a combination of treatment and research. This combination has continued to the present day. A human laboratory for the study of addiction phenomena such as conditioned responses was also founded in 1971. The key clinician investigators in this group have remained in the Center since the 1970s with most of the research staff continuing to work together. Important new investigators have been added over the years. Treatment was empirically based with randomized, controlled clinical trials as the gold standard for determining evidence-based treatment. The patients coming to treatment do not distinguish between abuse of alcohol and other drugs, so the treatment and research programs have always focused on all drugs including ethyl alcohol and the combination of ethyl alcohol with other drugs such as cocaine and opioids. Most of the patients coming for treatment also suffered from additional psychiatric disorders such as depression, anxiety, bipolar disorder or schizophrenia. Thus, the addiction treatment program in 1980 absorbed the rest of the VA Psychiatry Service into the Substance Abuse Program forming a new Behavioral Health Service with responsibility for over 9000 patients. The integration of substance abuse treatment with overall mental health care was the most efficient way to handle patients with complicated combinations of disorders. While this continues to be the best way to treat patients, it has proven difficult in practice. The main reason for this difficulty is that most mental health therapists whether they are psychiatrists, psychologists or social workers feel very inadequate to handle substance abuse problems. Unless they have had specialized training in addictive disorders, therapists are likely to be uncomfortable if substance abuse is one of the diagnoses while they may be quite comfortable treating other complex disorders such as schizophrenia. This lack of education of clinicians remains a major problem for our field. Some of the findings that came out of both the Penn/VA laboratory and clinical studies are now widely accepted and form the basis of standard clinical practice. These concepts and evidence will be briefly reviewed below.