The objective of this study was to evaluate the relationship between pesticide exposure and depression. A cross-sectional study was performed in a study population of 252 Greek male farmers using the Center for Epidemiological Studies Depression scale. Cumulative pesticide exposure was categorized in three mutually exclusive groups related to lifetime pesticide use: low (<275 days, the reference group), intermediate (276 to 1200 days), and high (>1200 days). Acute pesticide exposure was categorized in pesticide poisoning events and high pesticide exposure events. Multivariable logistic regression analysis was performed, and odds ratios, 95% confidence intervals, and P values were presented. After adjusting for confounding factors, a positive significant association was found between both high-exposure group and high pesticide exposure events and depressive symptoms. Apart from acute, high cumulative pesticide exposure may as well contribute to the development of depression.