Neisseria gonorrhoeae is a major cause of pelvic inflammatory disease, ectopic pregnancy, and infertility, and it can facilitate human immunodeficiency virus (HIV) transmission. Gonorrhea is the second most frequently reported communicable disease in the United States, with 361,705 reported cases in 2001. During the 1980s, gonococcal resistance to penicillin and tetracycline became widespread; as a result, CDC recommended using cephalosporins as first-line treatment for gonorrhea. Since 1993, CDC also has recommended using fluoroquinolones (i.e., ciprofloxacin, ofloxacin, or levofloxacin) for gonorrhea treatment. Fluoroquinolone therapy is used widely because it is a relatively inexpensive, oral, and single-dose therapy. However, fluoroquinolone-resistant N. gonorrhoeae (QRNG) is being identified more frequently. This report summarizes investigations of increases in QRNG in Hawaii and California in 2001 and provides data to support the recommendation that cephalosporins (i.e., ceftriaxone or cefixime) be used instead of fluoroquinolones as first-line treatment for gonorrhea acquired in these two states. The increases in QRNG highlight the importance of monitoring gonococcal resistance throughout the United States to guide local treatment decisions.