Angiotensin II (Ang II) plays a major role in the progression of myocardial hypertrophy to heart failure. Inhibiting the angiotensin converting enzyme (ACE) or blockade of the corresponding Ang II receptors is used extensively in clinical practice, but there is scope for refinement of this mode of therapy. This review summarizes the current understanding of the direct effects of Ang II on cardiomyocytes and then focus particularly on interaction of components of the renin-angiotensin system with other hormones and cytokines. New findings described in approximately 400 papers identified in the PubMed database and published during the 2.5 years are discussed in the context of previous relevant literature. The cardiac action of Ang II is influenced by the activity of different isoforms of ACE leading to different amounts of Ang II by comparison with other angiotensinogen-derived peptides. The effect of Ang II is mediated by at least two different AT receptors that are differentially expressed in cardiomyocytes from neonatal, adult and failing hearts. The intracellular effects of Ang II are influenced by nitric oxide (NO)/cGMP-dependent cross talk and are mediated by the release of autocrine factors, such as transforming growth factor (TGF)-beta1 and interleukin (IL)-6. Besides interactions with cytokines, Ang II is involved in systemic networks including aldosterone, parathyroid hormone and adrenomedullin, which have their own effects on cardiomyocytes that modify, amplify or antagonize the primary effect of Ang II. Finally, hyperinsulemia and hyperglycaemia influence Ang II-dependent processes in diabetes and its cardiac sequelae.