This study examines the impact of a work-skills program grounded in an integrated services approach on both employment and related life domains among homeless individuals. Six hundred thirty-eight participants in a 14-week work-skills program at a large day center in New England completed assessments at intake between 1999 and 2007; a subsample of 333 also completed assessments at graduation from the program; a smaller subsample of 55 participants were re-assessed 6 months after graduation. These assessments measured work and related life skills, employment, housing status, general health status, substance use, self-esteem and self-efficacy, and legal involvement. Results revealed improvement in all types of work and related life skills, employment and income, and multiple other life domains from baseline to graduation and follow-up. Exploratory analyses suggested that improvements in work and related life skills were associated with improvement in self-esteem and self-efficacy, and that these improvements predicted stable housing situations at follow-up. Overall, these findings indicate that, for individuals struggling with the challenges of homelessness, completion of a work-skills program has a positive impact on skills and employment, and on a diverse set of life domains.