Inflammation is an important component of the tumor microenvironment. IL-1 is an inflammatory cytokine which plays a key role in carcinogenesis and tumor progression. IL-1 is subject to regulation by components of the IL-1 and IL-1 receptor (ILR) families. Negative regulators include a decoy receptor (IL-1R2), receptor antagonists (IL-1Ra), IL-1R8, and anti-inflammatory IL-37. IL-1 acts at different levels in tumor initiation and progression, including driving chronic non-resolving inflammation, tumor angiogenesis, activation of the IL-17 pathway, induction of myeloid-derived suppressor cells (MDSC) and macrophage recruitment, invasion and metastasis. Based on initial clinical results, the translation potential of IL-1 targeting deserves extensive analysis.