There is growing evidence to support an important role of inflammation in the underlying pathophysiology of heart failure (HF). Indeed, inflammatory cytokine levels are well recognized to be increased in patients with left ventricular dysfunction and appear to have prognostic implications. Monocytes play a pivotal role in the inflammatory cascade and are a major source of both pro- and anti-inflammatory cytokines. They are intimately involved in tissue damage and repair and an imbalance of these processes may have detrimental consequences for the failing myocardium. Importantly, monocytes comprise of distinct subsets with different cell surface markers and functional characteristics and this heterogeneity may be important in understanding their specific role in HF. In HF, monocyte activation involves interplay between pattern recognition molecules, endotoxins, cytokines, and acute phase proteins. Activated monocytes migrate to the myocardium in response to powerful chemokines, where they must then attach to the endothelial wall before infiltrating into the myocardium itself. This review article aims to discuss the role of monocytes and inflammation in HF, focusing on monocyte activation, mobilisation, recruitment and endothelial adherence, as well as the effects they may have on myocardial performance. The therapeutic modulation of inflammation and monocyte activation in HF treatment will also be reviewed.