Using cluster detections drawn from the ROSAT all-sky survey and X-ray follow-up observations from Chandra and ROSAT, we obtain tight constraints on cluster scaling relations, dark energy, gravity at large scales, neutrino physics, and primordial non-Gaussianities. I will describe the novel statistical framework we employed to self-consistently and simultaneously constrain cosmology and observable-mass scaling relations accounting for survey biases, parameter covariances and systematic uncertainties. Combining cluster, CMB and galaxy clustering data we break strong degeneracies between model parameters. To further tighten the constraints on expansion we add Cepheid, supernova, and baryon acoustic oscillation data. For a spatially flat geometry, we obtain results that are in excellent agreement with GR+LCDM and represent the tightest and most robust simultaneous constraint on cosmic growth and expansion to date. Using cluster and CMB data and an analytic prescription for adding non-Gaussianity to the cluster mass function, we also constrain the amplitude of the skewness for two scenarios that have different overall levels of non-Gaussianity, characterized by how amplitudes of higher cumulants scale with the skewness. These are the first constraints on non-Gaussianity from large scale structure that can be usefully applied to any model of primordial non-Gaussianity. We find a sensitivity that implies that cluster counts could be used to distinguish qualitatively different models for the primordial fluctuations that have identical bispectra. I will review in detail all these results and highlight the power of X-ray cluster studies to constrain both astrophysics and cosmology.