Interpenetrating polymer networks (IPN) hydrogels have gained great attention in the last decades, mainly due to their biomedical applications. This review aims to give an overview of the recent design concepts of IPN hydrogels and their applications in controlled drug delivery, and separation processes. In the first part, the main strategies for the synthesis of semi-IPN and full-IPN hydrogels, their relevant properties, and biomedical applications are presented based on the nature of the networks, the main categories selected being: IPN hydrogels based on polysaccharides (chitosan, alginate, starch, and other polysaccharides), protein based IPN hydrogels, and IPN hydrogels based only on synthetic polymers. The influence of the second network on the stimuli responsiveness of the “smart” IPN hydrogels is discussed based on the most recent publications in the field. In the second part, an overview of the most specific applications of IPN hydrogels in separation processes is critically presented. Factors which control the separations of dyes and heavy metal ions by semi-IPN and full-IPN as novel sorbents are discussed based on the recently published articles and own results. A special concern is given to the macroporous IPN composite cryogels, which are very attractive materials for separation processes being endowed also with a high reusability.