Metaheuristics are techniques that use approximate and intuitive strategies to quickly find near-optimal solutions of complex optimization problems. A number of outstanding examples belong to evolutionary computation, the class of methods inspired to biological and evolutionary phenomena. These techniques have been extensively and successfully applied to feature-based image registration in medicine. However, with the increase in computational power during the last decade, intensity-based (or voxel-based) image registration methods have been preferred in many medical imaging applications, due to their robustness, accuracy and applicability, in cases where landmarks or other features are not available or easy to detect. While traditional numerical optimization techniques are employed to solve the registration problem, a number of contributions in the literature support the use of metaheuristics to overcome the shortcomings of classic methods. The aim of the paper is to review the state of the art in the application of evolutionary computation and other metaheuristics to intensity-based medical image registration. The study considers both well-know techniques with a large number of references in the literature as well as recent, outstanding proposals. The analysis focuses on the design of the methods to highlight common and successful practices. In addition, recommendations and open research lines in the field are provided. 2.1.1 Transformation model The transformation model determines which kind of geometrical transformation can be applied to the scene image to reach the model. This also controls which geometrical properties (e.g. size, shape, position, orientation, etc.) are preserved through the process. Common models include rigid transform, which allows translations and rotations, similarity transform, which also admits scaling, and affine transformation, which can also represent shearing. These are examples of global transformations having respectively 6, 7 and 12 degrees of freedom for 3D images. At the other end of the spectrum there are nonrigid (also called elastic) transformations, such as B-spline and thin-plate splines transformations, able to represent local deformations (warping) using hundreds or even thousands of parameters.