Calmodulin (CaM) is a calcium binding protein that regulates a wide range of enzymes. Recently the structures of a number of complexes between CaM and synthetic target peptides have been determined. The peptides correspond to the CaM-binding domain of skeletal and smooth muscle myosin light-chain kinase (MLCK) and calmodulin-dependent protein kinase II alpha. Comparison of the peptide-free and peptide-bound structures reveals that CaM undergoes a large conformational change when forming a complex, resulting in the formation of a binding surface that provides for an optimal interaction with its target. In this work, the available co-ordinates of the NMR solution structure of CaM-skeletal MLCK peptide are used as a basis upon which several molecular models of binding are built. The detailed features of the protein's peptide binding surface are revealed through two-dimensional topographical projections. Negatively charged margins at the binding surface extremities interact strongly with basic peptide residues separated by nine or ten positions. The binding surface core is hydrophobic and displays a groove with four deep pockets, which can accommodate bulky peptide residues at relative positions 4 and 8 (pocket A), 11 (pocket B), 13 (pocket C), 14 and 17 (pocket D). Therefore, both electrostatic and van der Waals' features contribute to the high affinity binding. A search for alternative peptide placements in the binding tunnel reveals the dominant role of specific electrostatic interactions in the binding energy. Apolar interactions are more permissive, such that the hydrophobic side-chains that line the binding tunnel adapt in order to maintain favourable van der Waals' contacts. The model suggests that the structure can accommodate large peptide translations (up to 5 A) and a reversed peptide binding mode, with a little loss in binding interaction energy. These calculations are compared with available experimental data, providing a structural rationale for the low sequence specificity of the CaM target recognition.