Individuals with medical conditions report more depressive symptoms than those without such conditions. This study assessed whether physical activity (PA) plays a mediational role in the association between medical conditions and depressive symptoms among Latino adults. Adjusting for socioeconomic factors, those who reported having been diagnosed with diabetes, cardio-related disease, hypertension, high cholesterol, arthritis, or sleep problems endorsed more symptoms of depression. Vigorous PA mediated the relation between depressive symptoms and hypertension. In other words, people with hypertension who engaged in vigorous PA reported less depressive symptoms. PA may be a promising avenue for improving hypertension and depressive symptoms.