Alternative splicing swells the coding capacity of the human genome, expanding the pharmacoproteome, the proteome that provides targets for therapy. Splicing, both constitutive and regulated forms, can itself be targeted by conventional and molecular therapies. This review focuses on splicing as a therapeutic target with a particular emphasis on molecular approaches. The review looks at the use of antisense oligonucleotides, which can be employed to promote skipping of constitutive exons, inhibit inappropriately activated exons, or stimulate exons weakened by mutations. Additionally this manuscript evaluates methods that reprogram RNAs using reactions that recombine RNA molecules in trans. Preliminary, but exciting, results in these areas of investigation suggest that these methods could eventually lead to treatments in heretofore intractable ailments.