Cobalt (Co) and its compounds are widely distributed in nature and are part of numerous anthropogenic activities. Although cobalt has a biologically necessary role as metal constituent of vitamin B12, excessive exposure has been shown to induce various adverse health effects. This review provides an extended overview of the possible Co sources and related intake routes, the detection and quantification methods for Co intake and the interpretation thereof, and the reported health effects. The Co sources were allocated to four exposure settings: occupational, environmental, dietary and medical exposure. Oral intake of Co supplements and internal exposure through metal-on-metal (MoM) hip implants deliver the highest systemic Co concentrations. The systemic health effects are characterized by a complex clinical syndrome, mainly including neurological (e.g. hearing and visual impairment), cardiovascular and endocrine deficits. Recently, a biokinetic model has been proposed to characterize the dose-response relationship and effects of chronic exposure. According to the model, health effects are unlikely to occur at blood Co concentrations under 300 μg/l (100 μg/l respecting a safety factor of 3) in healthy individuals, hematological and endocrine dysfunctions are the primary health endpoints, and chronic exposure to acceptable doses is not expected to pose considerable health hazards. However, toxic reactions at lower doses have been described in several cases of malfunctioning MoM hip implants, which may be explained by certain underlying pathologies that increase the individual susceptibility for Co-induced systemic toxicity. This may be associated with a decrease in Co bound to serum proteins and an increase in free ionic Co2+. As the latter is believed to be the primary toxic form, monitoring of the free fraction of Co2+ might be advisable for future risk assessment. Furthermore, future research should focus on longitudinal studies in the clinical setting of MoM hip implant patients to further elucidate the dose-response discrepancies.