Health care professionals are paramount to the prevention and management of suicidal thoughts and behaviors. Confidence in caring for people at risk of suicidal thoughts and behaviors is influenced by knowledge of and attitudes towards suicide. This systematic review aimed to explore health care professionals’ knowledge of and attitudes towards suicide, as well as, their confidence in caring for people at risk of suicidal thoughts and behaviors. A systematic search of 4 electronic databases over 10 years was conducted. Following retrieval of 1,723 abstracts, 46 primary research publications were included, involving both cross-sectional (n = 27) and intervention study designs (n = 19). Knowledge of, attitudes towards, and confidence in caring for people at risk of suicidal thoughts and behaviors were explored among primary health care professionals, specialists, and health care students. The influence of training and education, type of health care professional, country of practice, and prior experience with suicide were highlighted among included studies. Health care professionals’ knowledge of, attitudes towards and confidence in caring for people at risk of suicide are complex, interrelated constructs that shape their behaviors and may impact patient outcomes. Suicide training and education is necessary within health care curricula and as part of health care professionals’ continuing professional development.