Despite decades of research, cancer remains a devastating disease and new treatment options are needed. Today cancer is acknowledged as a multifactorial disease not only comprising of aberrant tumor cells, but also the associated stroma including tumor vasculature, fibrotic plaques and immune cells that interact in a complex heterotypic interplay. Myeloid cells represent one of the most abundant immune cell population within the tumor stroma and are equipped with a broad functional repertoire that promotes tumor growth by suppressing cytotoxic T cell activity, stimulating neo-angiogenesis and tissue remodeling. Therefore myeloid cells have become an attractive target for pharmacological intervention. In this review we summarize the pharmacological approaches to therapeutically target tumor-associated myeloid cells with a focus on advanced programs that are clinically evaluated. In addition, for each therapeutic strategy the preclinical rationale as well as advantages and challenges from a drug development perspective are discussed. This article is protected by copyright. All rights reserved.