Background: Research examining the impact of neighborhoods on asthma has shown an increased interest in the role of the psychosocial environment. We examined the associations between various measures of neighborhood safety, individual and family characteristics, and asthma outcomes among children in Los Angeles. Methods: Multilevel logistic regression models were used to analyze data on 3,114 children across 65 neighborhoods from Wave 1 of the Los Angeles Family and Neighborhood Survey (2000 to 2002). Primary caregivers reported asthma outcome and all individual covariates; home environmental characteristics were observed by the interviewer. Results: In fully adjusted models, parents who reported their neighborhood fairly safe or somewhat dangerous had lower odds of reported lifetime asthma compared to those who reported their neighborhood completely safe (OR 0.71; 95% CI 0.52-0.96 and OR 0.60; 95% CI 0.42-0.88 respectively). Conversely, parents who reported they could not trust their neighbors to keep their children safe had a nearly 40% increase in lifetime asthma compared to those who reported they could trust their neighbors to keep their children safe (OR 1.39; 95% CI 1.07-1.81). Conclusions: The study demonstrates a complex pattern between various measures of neighborhood safety and asthma and suggests that these relationships may operate differently in Los Angeles. As an increasing proportion of children are growing up in newer Western and Southwestern cities, which have different physical layouts and residential segregation patterns compared to Northeast and Midwestern cities, future studies should continue to examine neighborhood psychosocial stressors and asthma in diverse contexts.