This paper presents the application of an aerodynamic shape optimization methodology, Jetstream, to several cases in order to characterize the methodology and demonstrate its ability to solve challenging problems. In Jetstream, geometry parameterization and mesh movement are integrated by fitting the multi-block structured grids with B-spline volumes and applying mesh movement based on linear elasticity to the control points. Geometry control is achieved through either of two di↵erent approaches: using the B-spline surface control points as design variables, or embedding them into within a free-form deformation volume. Spatial discretization of the Reynolds-averaged Navier-Stokes equations is performed using summation-by-parts operators with simultaneous approximation terms at boundaries and block interfaces. The discrete equations are solved iteratively using a parallel Newton-Krylov-Schur algorithm. The discrete-adjoint method is used to calculate the gradients, which are supplied to a sequential quadratic programming optimization algorithm. The first drag minimization problem revisits the single-point lift-constrained drag minimization of the NASA Common Research Model (CRM) wing. Multimodality is studied on the CRM wing, beginning the same problem with a variety of di↵erent starting geometries. Results are also presented for the single-point CRM optimization with a 75% and a 100% minimum thickness constraint. The CRM wing-body-tail configuration is then optimized with a trim constraint and including the rotation of the horizontal stabilizer as a design variable. The second problem is a multipoint optimization of the RAE 2822 airfoil in transonic flow. The final two problems test the geometric flexibility and robustness of the aerodynamic optimization method. The first is a planform optimization of a rectangular NACA00012 wing in transonic, viscous flow. The second is a wing tip optimization of a planform based on the Boeing 737-900 wing. Overall, the results demonstrate that the algorithms adopted in Jetstream provide a reliable and e↵ective aerodynamic shape optimization methodology capable of addressing challenging problems involving substantial geometric changes.