Leukotriene　A4 (LTA4) hydrolase is a bifunctional zinc enzyme with the activities of epoxide hydrolase and amino peptidase. As an epoxide hydrolase, LTA4 hydrolase catalyzes the hydrolysis of LTA4 to leukotriene B4 (LTB4) which mainly functions as a chemoattractant and an activator of inflammatory cells. As an aminopeptidase, LTA4 hydrolase may process peptides related to inflammation and host defense. Therapeutic agents which selectively inhibit LTA4 hydrolase would block the formation of LTB4 and aminopeptidase activity and thus be potentially useful for the treatment of inflammation. Several approaches related to zinc-containing metalloproteinases led to the identification of captopril, bestatin, and kelatorphan as potent inhibitors of LTA4 hydrolase. This led to the design of a number of peptide and non-peptide analogs which contained potential zinc-chelating moieties, including thiols, hydroxamates, and norstatines. We found SA6541, which demonstrated good oral anti-inflammatory activity. In addition, SA6541 used in combination with cyclooxygenase (COX) inhibitors is more effective than SA6541 alone on inflammation. A more recent series of non-peptidic, non-zinc chelating inhibitors of LTA4 hydrolase has been reported. These inhibitors show anti-inflammatory activities in animal models. Recently, LTA4 hydrolase has been found to be overexpressed in some tumors as compared to normal tissues. Bestatin, one of the LTA4 hydrolase inhibitors, suppresses tumorigenesis in animal models and improved the 5-year survival rate in patients with lung carcinoma. It has been established that COX-2 is also overexpressed in some tumors and is important for tumorigenesis in humans. Based on our present knowledge, inhibitors of LTA4 hydrolase may be useful in combination with other agents such as COX inhibitors for the treatment of not only inflammation but also cancer.