Since April 15 and 17, 2009, when the first two cases of novel influenza A (H1N1) infection were identified from two southern California counties, novel influenza A (H1N1) cases have been documented throughout the world, with most cases occurring in the United States and Mexico. In the United States, early reports of illnesses associated with novel influenza A (H1N1) infection indicated the disease might be similar in severity to seasonal influenza, with the majority of patients not requiring hospitalization and only rare deaths reported, generally in persons with underlying medical conditions. As of May 17, 2009, 553 novel influenza A (H1N1) cases, including 333 confirmed and 220 probable cases, had been reported in 32 of 61 local health jurisdictions in California. Of the 553 patients, 30 have been hospitalized. No fatal cases associated with novel influenza A (H1N1) infection had been reported in California. This report summarizes the 30 hospitalized cases as of May 17, including a detailed description of four cases that illustrate the spectrum of illness severity and underlying risk factors. This preliminary overview indicates that, although the majority of hospitalized persons infected with novel influenza A (H1N1) recovered without complications, certain patients had severe and prolonged disease. All hospitalized patients with novel influenza A (H1N1) infection should be monitored carefully and treated with antiviral therapy, including patients who seek care >48 hours after illness onset.