Background: There is increasing evidence that healthcare workers (HCWs) experience significant psychological distress during an epidemic or pandemic. Considering the increase in emerging infectious diseases and the ongoing COVID-19 pandemic, it is timely to review and synthesize the available evidence on the psychological impact of disease outbreaks on HCWs. Thus, we conducted a systematic review to examine the impact of epidemics and pandemics on the mental health of HCWs. Method: PubMed, PsycInfo, and PsycArticles databases were systematically searched from inception to June-end 2020 for studies reporting the impact of a pandemic/epidemic on the mental health of HCWs. Results: Seventy-six studies were included in this review. Of these, 34 (45%) focused on SARS, 28 (37%) on COVID-19, seven (9%) on MERS, four (5%) on Ebola, two (3%) on H1N1, and one (1%) on H7N9. Most studies were cross-sectional (93%) and were conducted in a hospital setting (95%). Common mental health symptoms identified by this review were acute stress disorder, depression, anxiety, insomnia, burnout, and post-traumatic stress disorder. The associated risk factors were working in high-risk environments (frontline), being female, being a nurse, lack of adequate personal protective equipment, longer shifts, lack of knowledge of the virus, inadequate training, less years of experience in healthcare, lack of social support, and a history of quarantine. Conclusion: HCWs working in the frontline during epidemics and pandemics experience a wide range of mental health symptoms. It is imperative that adequate psychological support be provided to HCWs during and after these extraordinary distressful events.