Several SAMPL iterations have helped identify obstacles that need to be addressed and further studied, and are described in the literature . While work continues to seek to address these difficulties, new innovations have not always led to clear conclusions. In some cases, performance of a given method remains variable across several challenges. Particularly, performance has been highly variable by method and target, and until recently no method had emerged as universally reliable across all systems or most systems. In SAMPL7, several methods showed reasonable accuracy (RMSE under 3 kcal/mol) across multiple hosts, and one method had RMSE under 2 kcal/mol. In SAMPL8, we hope to see methods which perform reliably across multiple hosts, and determine whether any method(s) improve relative to prior challenges.