Molecular reorientations in rosuvastatin calcium, a drug that is widely used to prevent cardiovascular disease, were explored thoroughly by means of solid state nuclear magnetic resonance (1H and 13C NMR) combined with calculations of steric hindrances. The experimental results reveal rich internal reorientational dynamics. All relaxation processes were tested in a broad range of temperatures and described in terms of their type and the associated energy barriers. The internal molecular mobility of rosuvastatin calcium can be associated with the reorientational dynamics of four methyl groups, accompanied by reorientation of the isopropyl group. The energy barriers of methyl and isopropyl group reorientation depended on the type of E/Z isomers, while the water content also had a strong influence on the dynamics of the isopropyl group. In the paper, a consistent picture of the molecular dynamics is provided, facilitating our understanding of molecular mobility in this important pharmaceutical solid.