Nowadays, many modalities such as CT, X-ray scanners, MRI/fMRI, PET scan, etc. generate complex images with a large amount of data that are becoming extremely difficult to handle. This growing mass of data requires new strategies for the diagnosis of diseases and new therapies. In recent years, particular attention has been paid to computational intelligence methods in multimodal biomedical imaging applications. Inspired by artificial intelligence, mathematics, biology and other fields, these methods can find relationships between different categories of this complex data and provide a set of tools for the diagnosis and monitoring of the disease. This special issue provides a forum to publish original research papers covering the state-ofthe-art, new algorithms, methodologies, theories and implementations of computational intelligence methods for computer-aided diagnostic systems and multimodal biomedical imaging applications such as classification, restoration and registration.