Ionic substitutions have been proposed as a tool to improve the biological performance of calcium phosphate based materials. This review provides an overview of the recent results achieved on ion-substituted calcium phosphates prepared at low temperature, i.e. by direct synthesis in aqueous medium or through hydrolysis of more soluble calcium phosphates. Particular attention is focused on several ions, including Si, Sr, Mg, Zn and Mn, which are attracting increasing interest for their possible biological role, and on the recent trends and developments in the applications of ion-substituted calcium phosphates in the biomedical field.