Abstract: The weighted ensemble (WE) path sampling strategy orchestrates quasi-independent parallel simulations that are run with intermittent communication to enhance sampling of rare events such as large protein conformational transitions, protein folding, and protein binding. Trajectories are pruned or replicated in a way that encourages sampling of under-explored regions without biasing the dynamics. The WE strategy has been demonstrated to be orders of magnitude more efficient than standard simulations in generating complete pathways and rate constants for rare events of numerous benchmark systems. I will present advances in both WE methodology and software that have enabled applications to complex processes such as protein-protein binding along with challenges that remain.