As a common but understudied work setting, small and medium enterprises (SMEs) have been identified as a sector needing ‘special’ or ‘urgent’ attention in relation to occupational health research and practice (Cocker et al., Int J Mental Health Promot 1–18, 2013; Lindstrom, Social Prevent Med, 2004). However, they are known to be particularly challenging to engage in research, with owner/managers’ citing a lack of time to participate and a limited budget to implement programs (Eakin et al., Health Promot Pract 2(2):172–181, 2001). This chapter aims to highlight challenges associated with conducting occupational health intervention research with SMEs in relation to a specific mental health promotion intervention study, the Business in Mind Project. We focus on obstacles encountered in recruiting and retaining participants and propose related strategies to advance future research in this challenging but vital setting. Before discussing issues in study implementation, we provide a brief overview of the study but direct readers seeking a detailed account of the project rationale and design to the study protocol (Martin et al., BMC Public Health 9(239), 2009).