INTRODUCTION. There has been some recent concern regarding possible systemic health effects resulting from elevated blood cobalt concentrations in patients with cobalt containing hip implants. To date there are no blood cobalt criteria to help guide physicians when evaluating an individual hip implant patient's risk of developing systemic health effects because historically there was little or no concern about systemic cobalt toxicity in implant patients. OBJECTIVE. Our purpose is to describe recently completed research regarding the relationship between blood cobalt concentrations and clinical health effects. We discuss the possibility of systemic health effects in patients with metal containing implants and propose various blood cobalt concentrations that are not associated with an increased risk of developing certain adverse effects. METHODOLOGY. The primary literature search was conducted using PubMed and Web of Science using the following search terms: cobalt AND (toxicity OR health effects OR cardiotoxicity OR hematological OR endocrine OR immunological OR reproductive OR testicular effects OR neurological OR case report OR cohort OR Roncovite). The searches identified 6786 papers of which 122 were considered relevant. The Agency for Toxic Substances and Disease Registry toxicological profile for cobalt and the U.S. Environmental Protection Agency Office of Research and Development's National Center for Environmental Assessment's documentation on the provisional peer-reviewed toxicity value for cobalt were also utilized to identify secondary literature sources. RESULTS. Our review of the toxicology and medical literature indicates that highly elevated blood cobalt concentrations can result in certain endocrine, hematological, cardiovascular, and neurological effects in animals and/or humans. These studies, in addition to historical clinical findings involving the therapeutic use of cobalt, indicate that significant systemic effects of cobalt will not occur below blood cobalt concentrations of 300 μg/L in most persons. Some individuals with specific risk factors for increased susceptibility (e.g., severe and sustained hypoalbuminemia) may exhibit systemic effects at lower cobalt blood concentrations. This review also describes several cobalt dosing studies performed with human volunteers that consumed cobalt for 15, 30, or 90 days. Overall, the results of these dosing studies indicate that sustained blood cobalt concentrations averaging 10-70 μg/L for up to 90 days cause no significant clinical effects (maximum concentrations approached 120 μg/L). Some proposed blood criteria for assessing implant wear and local tissue damage have been suggested by several medical groups. For example, the UK Medicines and Healthcare Products Regulatory Agency has proposed a blood cobalt guidance value of 7 μg/L, and the Mayo Clinic has suggested serum cobalt concentrations greater than 10 μg/L, but both of these values are primarily intended to address implant wear and to alert physicians to the possibility of an increased incidence of local effects. There is a clear lack of consensus regarding how to identify a specific numerical blood concentration of concern and whether whole blood or serum is a better matrix to assess total cobalt concentration. CONCLUSIONS. Based on currently available data, only under very unusual circumstances should a clinician expect that biologically important systemic adverse effects might occur in implant patients with blood cobalt concentrations less than 300 μg/L. Patients with metal-containing hip implants who exhibit signs or symptoms potentially related to polycythemia, hypothyroidism, neurological, or cardiac dysfunction should be clinically evaluated for these conditions. Polycythemia appears to be the most sensitive endpoint.