Pre-mRNA splicing is catalyzed by two unique spliceosomes, designated U2- or U12-dependent. In contrast to the well-characterized U2-dependent spliceosome, much remains to be learned about the less abundant U12-type spliceosome. This review focuses on recent advances in elucidating the structure and function of the minor U12-dependent spliceosome. Interesting similarities and differences between the U12- and U2-dependent spliceosomes are also highlighted.