Leukocytes such as neutrophils and macrophages play a fundamental role in host defence and likely contribute to tissue damage associated with chronic inflammatory diseases (e.g., emphysema, bronchitis, rheumatoid arthritis, inflammatory bowel disease, etc). Apoptosis or programmed cell death is a key process regulating inflammatory cell survival providing an efficient non-inflammatory mechanism for removal of potentially histotoxic cells from inflamed sites by resident or recruited macrophages and is critically involved in the successful resolution of inflammation. Recent findings have demonstrated how neutrophil apoptosis as well as macrophage phagocytosis of apoptotic cells can be regulated pharmacologically suggesting that selective interference of these fundamental processes may be harnessed for therapeutic gain. Signalling pathways, including those involving transcription factors (e.g., NF-κB) and kinases (e.g., MAPK and PI3K) have been shown to be key regulators of inflammatory cell survival and apoptosis in vitro. In addition, manipulation of such pathways in vivo has indicated that they are also involved in the resolution of inflammation. Furthermore, manipulation of proteins directly involved in the control of apoptosis such as Bcl-2 family members and caspases can also be targeted in vivo to influence inflammatory resolution. Recently, it has been shown that cyclin-dependent kinase (CDK) inhibitor drugs, under development for the treatment of cancer, induce caspase-dependent human neutrophil apoptosis possibly by altering levels of the anti-apoptotic Bcl-2 family member, Mcl-1. Importantly, the CDK inhibitor drugs augment the resolution of established ‘neutrophil dominant’ models of inflammation (including pleurisy, pulmonary fibrosis and arthritis) by promoting apoptosis of neutrophils. Thus in this presentation I will discuss how manipulation of apoptotic pathways together with ensuring macrophage clearance of apoptotic cells appear to be viable pharmacological targets for driving the resolution of inflammation.