Weight gain is an adverse effect of antidepressants and antipsychotics. This side effect can lead to numerous comorbidities and reduces life expectancy. The use of these drugs is increasing worldwide, and the weight gain produced by them represents a common clinical challenge. The goal of this systematic review was to evaluate the potential association of antidepressant and antipsychotic therapy with body weight gain in cohort studies. A search of cohort studies investigating the association between weight gain and the use of antidepressants and antipsychotics in individuals was conducted through the PubMed database from 1 January 2008 to 31 January 2019 following the PRISMA statement. We found 27 independent eligible cohort studies that included children (2-18 years old) and adult (18-103 years old) subjects. Most of the included studies showed a 5% weight gain in individuals using antidepressant therapy. However, Quetiapine, Haloperidol, Trifluoperazine, Risperidone, Aripiprazole, Olanzapine, and Clozapine increased body weight >= 7% from baseline, which is considered a clinically significant result. Weight loss was found in individuals treated with Bupropion. Further cohort studies with higher sample sizes and longer durations of treatment are needed to confirm our observations.