Attending college can be a stressful time for many students. In addition to coping with academic pressure, some students have to deal with the stressful tasks of separation and individuation from their family of origin while some may have to attend to numerous work and family responsibilities. In this context, many college students experience the first onset of mental health and substance use problems or an exacerbation of their symptoms. Given the uniqueness of college students, there is a need to outline critical issues to consider when working with this population. In this commentary, first, the prevalence of psychiatric and substance use problems in college students and the significance of assessing age of onset of current psychopathology are described. Then, the concerning persistent nature of mental health problems among college students and its implications are summarized. Finally, important aspects of treatment to consider when treating college students with mental health problems are outlined, such as the importance of including parents in the treatment, communicating with other providers, and employing of technology to increase adherence. It is concluded that, by becoming familiar with the unique problems characteristic of the developmental stage and environment college students are in, practitioners will be able to better serve them.