This article is the second part of a systematic review of studies on occupational therapy-related intervention for people with multiple sclerosis (MS). The objective of this systematic review was to critically appraise and synthesize the applicable findings to address the following focused question: What is the evidence for the effectiveness of interventions within the scope of occupational therapy practice for people with multiple sclerosis? Part 1 (Yu & Mathiowetz, 2014) reviewed evidence for the effectiveness of activity- and participation-based interventions for people with MS. In contrast to the top-down approach, enabling occupational performance can be achieved through remediating impaired personal abilities. Therefore, Part 2 focuses on occupational therapy interventions targeting impairment. Studies included in this review focused on improving client factors and performance skills in people with MS, including cognition, emotional regulation, and motor and praxis skills.