Escalating costs of semiconductor technology and its lagging performance relative to historic trends is motivating acceleration and specialization as more impactful means to increase system value. Targeted specialization is being increasingly pursued as an important way to achieve dramatic improvements in workload acceleration. This requires a broad understanding of workloads, system structures, and algorithms to determine what to accelerate / specialize, and how, i.e., via SW?; via HW?; or via SW+HW? which presents many choices, necessitating co-optimization of SW and HW. In this talk, we will focus on an application driven approach to software and system co-optimization, based on inventing new software algorithms, that have strong affinity to hardware acceleration. A High Level design methodology that is needed to enable targeted specialization in hardware will also be described.