Over the past several decades, memory technologies have exploited continual scaling of CMOS to drastically improve performance and cost. Unfortunately, charge-based memories become unreliable beyond 20 nm feature sizes. A promising alternative is Phase-Change-Memory (PCM) which leverages scalable resistive thermal mechanisms. To realize PCM's potential, a number of challenges, including the limited wear-endurance and costly writes, need to be addressed. This thesis introduces novel methodologies for encoding data on PCM which exploit asymmetries in read/write performance to minimize memory's wear/energy consumption. First, we map the problem to a distance-based graph clustering problem and prove it is NP-hard. Next, we propose two different approaches: an optimal solution based on Integer-Linear-Programming, and an approximately-optimal solution based on Dynamic-Programming. Our methods target both single-level and multi-level cell PCM and provide further optimizations for stochastically-distributed data. We devise a low overhead hardware architecture for the encoder. Evaluations demonstrate significant performance gains of our framework.