Lipoxins were discovered 40 years ago, and since then, their beneficial roles for human health have been confirmed in numerous studies. These small molecules belong to the eicosanoid class of compounds, which are generated metabolically by lipoxygenases. Lipoxins are released during various diseases and conditions, including but not limited to systemic inflammation, infection, asthma, cancer, diabetes, and cardiovascular disorders. Recently, several synthetic lipoxin analogs have been developed that also exhibit potent anti-inflammatory properties. In this review, we discuss the inflammation-resolving roles of lipoxins in various major diseases. Further, we summarize the latest reports on the use of synthetic lipoxins as potential therapeutic agents and discuss the role of aspirin-dependent lipoxin production in alleviating various diseases, including cancer.