The past two decades have witnessed several paradigm shifts in computing environments. Starting from cloud computing which offers on-demand allocation of storage, network, compute, and memory resources, as well as other services, in a pay-as-you-go billingmodel. Ending with the rise of permissionless blockchain technology, a decentralized computing paradigm with lower trust assumptions and limitless number of participants. Unlike in the cloud, where all the computing resources are owned by some trusted cloud provider, permissionless blockchains allow computing resources owned by possibly malicious parties to join and leave their network without obtaining permission from some centralized trusted authority. Still, in the presence of malicious parties, permissionlessblockchain networks can perform general computations and make progress. Cloud computing is powered by geographically distributed data-centers controlled and managed by trusted cloud service providers and promises theoretically infinite computing resources. On the other hand, permissionless blockchains are powered by open networks of geographically distributed computing nodes owned by entities that are not necessarily known or trusted. This paradigm shift requires a reconsideration of distributed data management protocols and distributed system designs that assume low latency across system components, inelastic computing resources, or fully trusted computing resources.In this dissertation, we propose new system designs and optimizations that address scalability and efficiency of distributed data management systems in cloud environments. We also propose several protocols and new programming paradigms to extend the functionality and enhance the robustness of permissionless blockchains. The work presented spans global-scale transaction processing, large-scale stream processing, atomic transaction processing across permissionless blockchains, and extending the functionality and the use-cases of permissionless blockchains. In all these directions, the focus is on rethinking system and protocol designs to account for novel cloud and permissionless blockchain assumptions. For global-scale transaction processing, we propose GPlacer, a placement optimization framework that decides replica placement of fully and partial geo-replicated databases. For large-scale stream processing, we propose Cache-on-Track (CoT) an adaptive and elastic client-side cache that addresses server-side load-imbalances that occur in large-scale distributed storage layers. In permissionless blockchain transaction processing, we propose AC3WN, the first correct cross-chain commitment protocol that guarantees atomicity of cross-chain transactions. Also, we propose TXSC, a transactional smart contract programming framework. TXSC provides smart contract developers with transaction primitives. These primitives allow developers to write smart contracts without the need to reason about the anomalies that can arise due to concurrent smart contract function executions. In addition, we propose a forward-looking architecture that unifies both permissioned and permissionless blockchains and exploits the running infrastructure of permissionless blockchains to build global asset management systems
