We present a machine learning approach called shape regression machine (SRM) to segmenting in real time an anatomic structure that manifests a deformable shape in a medical image. Traditional shape segmentation methods rely on various assumptions. For instance, the deformable model assumes that edge defines the shape; the Mumford-Shah variational method assumes that the regions inside/outside the (closed) contour are homogenous in intensity; and the active appearance model assumes that shape/appearance variations are linear. In addition, they all need a good initialization. In contrast, SRM poses no such restrictions. It is a two-stage approach that leverages (a) the underlying medical context that defines the anatomic structure and (b) an annotated database that exemplifies the shape and appearance variations of the anatomy. In the first stage, it solves the initialization problem as object detection and derives a regression solution that needs just one scan in principle. In the second stage, it learns a nonlinear regressor that predicts the nonrigid shape from image appearance. We also propose a boosting regression approach that supports real time segmentation. We demonstrate the effectiveness of SRM using experiments on segmenting the left ventricle endocardium from an echocardiogram of an apical four chamber view.