Background: Trimethoprim has been recently implicated in the development of hyperkalemia when administered at standard doses to immunocompetent patients. However, many clinicians are unaware of this potentially dangerous adverse effect. Objective: To review reported cases of trimethoprim-induced hyperkalemia in immunocompetent patients and identify predisposing factors, treatment, and outcome. Methods: A MEDLINE literature search was performed using the key words ‘trimethoprim’ and ‘hyperkalemia’. All English-language case reports and bibliographies of immunocompetent patients with trimethoprim-induced hyperkalemia were reviewed. Results: Nine cases were identified. The mean patient age was 77.6 years, and the mean duration of therapy was 10.2 days. Seven patients received standard oral dosages of trimethoprim-sulfamethoxazole for common infections, and 2 patients were concurrently receiving angiotensin-converting enzyme inhibitors. The mean pretreatment levels of creatinine and potassium were 1.01 mg/dl and 4.55 mmol/l, respectively. The mean peak serum potassium level was 7.0 mmol/l. No deaths attributable to hyperkalemia occurred. Conclusions: Hyperkalemia due to trimethoprim typically affects elderly patients administered standard oral dosages, even in the presence of a normal serum creatinine level. Concurrent angiotensin-converting enzyme inhibitor therapy may increase the risk of hyperkalemia. The prognosis is favorable with standard therapy for hyperkalemia and withdrawal of trimethoprim.