Purpose Flexible work arrangements are growing in order to develop resource-efficient production and because of advanced technologies, new societal values, changing demographics, and globalization. The article aims to illustrate the emerging challenges and opportunities for work disability prevention efforts among workers in alternate work arrangements. Methods The authors participated in a year-long collaboration that ultimately led to an invited 3-day conference, "Improving Research of Employer Practices to Prevent Disability," held October 14-16, 2015, in Hopkinton, Massachusetts, USA. The collaboration included a topical review of the literature, group conference calls to identify key areas and challenges, drafting of initial documents, review of industry publications, and a conference presentation that included feedback from peer researchers and a roundtable discussion with experts having direct employer experience. Results Both worker and employer perspectives were considered, and four common alternate work arrangements were identified: (a) temporary and contingent employment; (b) small workplaces; (c) virtual work/telework; and (d) lone workers. There was sparse available research of return-to-work (RTW) and workplace disability management strategies with regard to alternate work patterns. Limited research findings and a review of the grey literature suggested that regulations and guidelines concerning disabled workers are often ambiguous, leading to unsatisfactory protection. At the workplace level, there was a lack of research evidence on how flexible work arrangements could be handled or leveraged to support RTW and prevent disability. Potential negative consequences of this lack of organizational guidance and information are higher costs for employers and insurers and feelings of job insecurity, lack of social support and integration, or work intensification for disabled workers. Conclusions Future studies of RTW and workplace disability prevention strategies should be designed to reflect the multiple work patterns that currently exist across many working populations, and in particular, flexible work arrangements should be explored in more detail as a possible mechanism for preventing disability. Labor laws and policies need to be developed to fit flexible work arrangements.