Microphthalminae Hartmann-Schröder, 1971 was proposed in Hesionidae to include Microphthalmus and Hesionides; however, the affinities of these genera to other members of Hesionidae have been debated, and some authors have concluded they do not belong in Hesionidae. Herein, based on morphological characters, a phylogenetic analysis of the subfamily and some other similar poorly-known genera, with an uncertain position in Hesionidae was performed to clarify their affinities. Our results indicate that Microphthalminae, as currently delimited, is paraphyletic. The inclusion of Struwela, Uncopodarke, and Westheideius, a new genus, as well as the recognition of Fridericiella are proposed to meet the requirement of monophyly; and as result of this, the elevation in rank to the family level is herein presented. Furthermore, the type species for Hesionella and Struwela are redescribed, and a new species in the latter is described. A key to identify microphthalmid genera is also included.