Ongoing evidence has suggested the role of male factor infertility as a potential predictor of mortality and general health status. The aim of the present review is to update the current knowledge base regarding the association between male factor infertility and general health through a critical review of the literature. A systematic review of the literature was carried out from inception to November 2019 in order to evaluate significant associations between male infertility and adverse health outcomes such as cardiovascular, oncologic, metabolic and autoimmune diseases as well as overall mortality. In all, 27 studies met inclusion criteria and were critically examined. Five studies examined male infertility and cardiovascular disease risk, 11 examined oncologic risk (e.g., overall cancer risk, testis and prostate cancer), 8 examined aggregate chronic medical diseases and 5 infertility related to incidence of mortality, for a total of 599,807 men diagnosed with any male factor infertility covering a period from 1916 to 2016. A man's fertility and overall health appear to be interconnected. Therefore, a diagnosis of male infertility may allow a window into future comorbidity and/or mortality which may help guide clinical decisions and counseling. Several possible etiologies such as genetic, epigenetic, developmental, and lifestyle-based factors need to be further evaluated in order to establish the underlying mechanisms between male infertility and health.