A summary of all existing information collected since 1980 on contaminants in tilapia from the Salton Sea is presented and risks to humans and fish-eating birds assessed. Of the 17 trace elements, 42 organic pesticides and 48 polychlorinated biphenyls (PCBs) analyzed in tilapia whole body and fillet samples, only selenium (Se), arsenic (As) and possibly dichlorodiphenyltrichloroethane (DDE) were found at levels high enough to be of concern for fish, birds or humans. Average current concentration of arsenic (As) was 0.7 µg g−1 wet weight (ww) in whole body samples and 1.2 µg g−1 ww in fillet samples, or 2.8 and 5.7 µg g−1 dry weight (dw), respectively. Inorganic As averaged 0.006 µg g−1 ww (0.03 µg g−1 dw) in fillet samples, which represented 0.3% of total As. By U.S. Environmental Protection Agency (U.S.EPA) guidelines, As levels in tilapia pose no threat of non-cancerous adverse health effects in children and adults. As is a known human carcinogen, however, and U.S.EPA cancer risk assessment procedures indicate that a weekly consumption of 540 g (19 oz) or more for 70 years would increase the upper bound cancer risk by 1 in 100,000 consumers exposed. Average current Se concentration was 2.2 µg g−1 ww in tilapia whole body samples and 1.9 µg g−1 ww in fillet (8.3 and 9 µg g−1 dw, respectively). Consumption of Se-contaminated tilapia was found to present no unacceptable risk for adverse health effects for adults consuming up to 1000 g (35 oz) of fillet per week even when additional intakes of Se from other food items were taken into account. Similarly, children weighing 30 kg or more could safely eat up to 430 g (15 oz) of tilapia fillet on a weekly basis. A health advisory issued by the State of California in 1986 recommended, on the basis of Se levels, that consumption of any fish from the Salton Sea be limited to 114 g (4 oz) every 2 weeks, but the rationale and calculations on which that advisory was based are unavailable. We suggest that the existing health advisory for Salton Sea tilapia be revised by the state in light of this new information and updated risk parameters for As and Se. Dichlorodiphenyltrichloroethane (DDE) was detected in all samples of tilapia, with current levels averaging 0.085 µg g−1 in whole tilapia and 0.032 µg g−1 in fillet ww. Compared to screening values proposed by the U.S. EPA, these concentrations are unlikely to cause non-cancerous health effects in anglers, but one might exceed a 1 × 10−5 increase in cancer risk by consuming more than 4 meals of tilapia per week. Similarly, polychlorinated biphenyls (PCBs) were detected in tilapia fillets at levels that may increase the cancer risk for those anglers also eating more than 4 meals of tilapia per week. These determinations are based, however, on DDE concentrations reported from a small sample size (n = 4), and on screening values recommended by U.S.EPA. The paucity of DDE and total DDT analyses carried out in recent times on the edible portion of Salton Sea tilapia warrants additional analyses in order to evaluate the need for issuance of a fish consumption advisory with regards to long term exposure to total DDT via consumption of Salton Sea fish. With regards to the potential impact on fish and piscivorous birds, we cannot conclude whether concentrations of As in tilapia could pose a threat to the fish and the birds feeding on them. Se concentrations, however, may be elevated enough to negatively affect fish health, and reproduction and immune systems of piscivorous birds, but definitive studies are lacking. Total DDT and PCB concentrations in whole tilapia are not elevated enough to have adverse effects on fish and piscivorous birds. Fish harvesting for fish meal production has been proposed for the Salton Sea. Based on whole fish dry weight values of 61% protein and 21% ash, and the determined contaminant levels, tilapia could yield a meal of reasonable quality for use in formulating poultry, livestock and aquaculture feeds.