A number of recent studies have highlighted that splicing is frequently altered in cancer and that mutations affecting splicing of key cancer-associated genes as well as mutations and copy-number changes affecting spliceosomal proteins themselves are enriched in cancer. In parallel, there is also accumulating evidence that several molecular subtypes of cancer are highly dependent on wildtype splicing function for cell survival. These findings have resulted in a growing interest in targeting splicing catalysis, splicing regulatory proteins, and/or individual key altered splicing events in the treatment of cancer. In this review we present strategies that exist and are in development to target altered dependency on the spliceosome as well as aberrant splicing in cancer. These include drugs to target global splicing in cancer subtypes which are preferentially dependent on wildtype splicing for survival, methods to alter post-translational modifications of splice regulatory proteins, and strategies to modulate pathologic splicing events and protein/RNA interactions in cancer.