Introduction Taxi drivers experience frequent hassles that may contribute to mental exertion and depression symptoms. Aim Mental exertion and depression symptoms in taxi drivers are explored in association with hassles, effort‐reward imbalance, job strain, and iso‐strain. Methods Personal interviews were conducted with 130 drivers in San Francisco. Results Mental exertion averaged 4.5 (±2.68) and physical exertion averaged 3.71 (±2.1) on 0 to 10 Borg scales. Based on the Center for Epidemiological Studies‐Depression scale, 38% had depression symptoms. Mental exertion and depression symptoms correlated with job strain, iso‐strain and effort‐reward imbalance in anticipated directions, lending construct validity to the Borg mental exertion scale. Physical exertion, night shift, stressful personal events, and being uninsured for healthcare predicted mental exertion. Lack of respect by dispatchers and stressful personal events predicted depression symptoms. Conclusion Selected hassles may be remedied by communication trainings, emphasizing mutual respect. Recognition and treatment of depression in taxi drivers are important.