We discuss the design and the implementation of Locus, a system and a language to orchestrate the optimization of applications. The increasing complexity of machines and the large space of program variants, produced by the many transformations available, conspire to make compilers deliver unsatisfactory performance. As a result, optimization experts must intervene to manually explore the space of program variants seeking the best version for each target machine. This intervention is unproductive, and maintaining and managing sequences of transformations as new architectures are adopted and new application features are incorporated is challenging.Locus allows collections of program transformation sequences to be specified separately from the application code. The language is able to represent in a clear notation complex collections of transformations that are applied to code regions selected by the programmer. The system integrates multiple optimization modules as well as search modules that facilitate the efficient traversal of the space of program variants. Locus is intended to help experts in the optimization process, specially for complex, long-lived applications that are to be executed on different environments. Four examples are presented to illustrate the power and simplicity of the language. Although not the primary focus of this paper, the examples also show that exploring the space of variants typically leads to better performing codes than those produced by conventional compiler optimizations that are based on heuristics.