Metronidazole is a treatment of choice for several types of infections, but coexisting conditions or concomitant medications may preclude its use. Although tinidazole, a newer nitroimidazole, may be an option in cases where drug interactions make the use of metronidazole inadvisable, similar absolute contraindications exist. In situations where nitroimidazole use is contraindicated or inadvisable, clinicians may have difficulty deciding on efficacious treatment options. For the treatment of trichomoniasis, alternatives include furazolidone, clotrimazole, nonoxynol-9 or paromomycin. Alternatives for bacterial vaginosis include clindamycin topically or systemically. For giardiasis, alternative options include paromomycin, nitazoxanide or the antihelminthic benzimidazoles. Alternatives for Clostridium difficile are varied, including oral vancomycin, nitazoxanide and rifaximin. Although options are limited, alternative therapies for treatment of patients with absolute contraindications to the nitroimidazole antibiotics are available.