The recent discovery of the Spectre and Meltdown attacks represents a watershed moment not just for the field of Computer Security, but also of Programming Languages. This paper explores speculative side-channel attacks and their implications for programming languages. These attacks leak information through micro-architectural side-channels which we show are not mere bugs, but in fact lie at the foundation of optimization. We identify three open problems, (1) finding side-channels, (2) understanding speculative vulnerabilities, and (3) mitigating them. For (1) we introduce a mathematical meta-model that clarifies the source of side-channels in simulations and CPUs. For (2) we introduce an architectural model with speculative semantics to study recently-discovered vulnerabilities. For (3) we explore and evaluate software mitigations and prove one correct for this model. Our analysis is informed by extensive offensive research and defensive implementation work for V8, the production JavaScript virtual machine in Chrome. Straightforward extensions to model real hardware suggest these vulnerabilities present formidable challenges for effective, efficient mitigation. As a result of our work, we now believe that speculative vulnerabilities on today’s hardware defeat all language-enforced confidentiality with no known comprehensive software mitigations, as we have discovered that untrusted code can construct a universal read gadget to read all memory in the same address space through side-channels. In the face of this reality, we have shifted the security model of the Chrome web browser and V8 to process isolation.