Calmodulin (CaM), the prototypical calcium sensing protein in eukaryotes, comprises two domains separated by a short flexible linker, which allows CaM to assume a wide range of extended and compact conformations. Here we use NMR relaxation measurements to explore the role of the linker in CaM function and dynamics. Using paramagnetic relaxation enhancement (PRE) measurements, we examine the effect of changes in the length and rigidity of the linker on the transient association between the two domains of Ca2+-bound CaM (CaM-4Ca(2+)). We observe that transient interdomain association, represented by an effective molarity (M-eff), is maximal for a linker extended by one residue from the wild-type length and decreases for lengths longer or shorter than that. The results can be quantitatively rationalized using a simplified model of a random coil whose two ends must be a specific distance apart for an interaction to occur. The results correlate well with the affinity of CaM-4Ca(2+) for a target peptide, suggesting that the transient compact states adopted by CaM-4Ca(2+) in the absence of peptide play a direct role in facilitating target binding.