Translocations involving the anaplastic lymphoma kinase (ALK) gene locus on chromosome 2p23 were first described in anaplastic large cell lymphoma (ALCL). Although most commonly fused to the nucleophosmin (NPM1) gene on chromosome 5q35, which results in the t(2;5)(p23;q35)/NPM1-ALK translocation, several other ALK translocation partners have meanwhile been identified. Furthermore, apart from ALCL, ALK-involving translocations have been described in other hematopoietic and non-hematopoietic cancers. However, despite a rapid increase in literature on the nature and tissue distribution of ALK-translocations, much less is known about the mechanisms of formation of these translocations. The emergence of translocations has been linked to the transcriptional activity of the respective genome regions, reorganization of the chromatin and activation of the DNA repair machinery. In this review we discuss mechanisms and implications of formation of ALK-translocations.