Background: There is a need to better understand the depression phenomenon and to clarify why some students become depressed and others don't. The purpose of this study was to compare the prevalence of depressive symptoms among health professions' (HP) students, and to explore the association between socio-demographic factors (e.g. year of study, discipline, gender) and depressive symptoms. Methods: In this descriptive-analytic, cross-sectional study, stratified proportionate sampling strategy was used to select the study sample during the academic year 2012-2013. The students from four health professions' schools situated within a large, public university located in Riyadh, Saudi Arabia were screened for depressive symptoms using the 21-item Beck Depression Inventory (BDI II). Chi-square test, student t-test and ANOVA were used to compare different categorical variables. Results: The overall response rate was 79.0 %, the highest among dental students 86.1 %, and lowest among nursing (49.7 %). The overall prevalence rate of depressive symptoms was 47.0 %; it was highest among dentistry students (51.6 %), followed by medicine (46.2 %), applied medical sciences (AMS) (45.7 %) and lowest among nursing students (44.2 %). A statistically significant association was found between the presence and severity of depressive symptoms on one hand and the female gender (p = 0.000) and year of study on the other hand. Conclusion: This study seems to indicate an alarming rate of depressive symptoms. Female gender, dentistry, the third year for all schools and fifth year for medicine and dentistry have the highest association with depressive symptoms. Future studies may be needed to explore further the reasons and explanations for the variation in the prevalence of depressive symptoms among these groups. The factors that deserve exploration include curricular variables and personal factors such as the students' study skills.