Skin infection secondary to gram-negative organisms is uncommon and is typically limited to persons who are immunocompromised. When these do occur, they are acute, progressive, and severe. Here we report 2 cases of painful red nodules that presented with a waxing and waning course over a long period. One case is that of a 45-year-old healthy white man who developed Serratia marcescens infection in 1 leg. The other case is that of a 78-year-old man with chronic lymphocytic leukemia treated with prednisone who developed infection of the leg secondary to Pseudomonas aeruginosa. In the first case, symptoms were present for 2 years before definitive diagnosis and treatment. In the second case, 4 months elapsed. Ultimately, both patients responded to antibiotic therapy and recovered. These cases illustrate an unusual presentation of chronic red painful nodules of the leg secondary to infection with gram-negative organisms and underscore the importance of culture even when infection seems unlikely.