Neurofibromatosis type two (NF2) is a genetic disorder predisposing those affected to the development of multiple benign tumors in their central and peripheral nervous systems. This is due to the absence of the tumor suppressor protein merlin, which is encoded by the NF2 gene. In nearly all NF2 cases, patients present with bilateral schwannomas of the vestibulocochlear nerve, in addition to other schwannomas throughout the central and peripheral nervous systems, as well as meningiomas and ependymomas. Currently, no therapeutic alternatives to surgical removal and radiation therapy are available for NF2 patients. This study investigated cobimetinib, an inhibitor of the often-deregulated mitogen activated protein kinase (MAPK) pathway in NF2 tumors, and its in vitro mechanism of action in both mouse and human NF2 schwannoma model cell lines. It was demonstrated that the drug decreased 70% and 60% of the viability at 10μM in the mouse and human merlin-deficient cell lines, respectively. It was further demonstrated that this decrease in viability was due to cytostatic and cytotoxic effects of cobimetinib in the case of the mouse NF2 schwannoma model but only due to cytostatic effects of cobimetinib in the human NF2 schwannoma model. These results show promise in targeting the MAPK pathway in NF2 tumors, and the promise of cobimetinib specifically, supporting further cytometric flow and in vivo testing of the inhibitor.