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The central task in many interactive machine learning systems can be formalized as the sequential optimization of a black-box function. Bayesian optimization (BO) is a powerful model-based framework for \emph{adaptive} experimentation, where the primary goal is the optimization of the black-box function via sequentially chosen decisions. In many real-world tasks, it is essential for the decisions to be \emph{robust} against, e.g., adversarial failures and perturbations, dynamic and time-varying phenomena, a mismatch between simulations and reality, etc. Under such requirements, the standard methods and BO algorithms become inadequate. In this dissertation, we consider four research directions with the goal of enhancing robust and adaptive decision making in BO and associated problems. First, we study the related problem of level-set estimation (LSE) with Gaussian Processes (GPs). While in BO the goal is to find a maximizer of the unknown function, in LSE one seeks to find all "sufficiently good" solutions. We propose an efficient confidence-bound based algorithm that treats BO and LSE in a unified fashion. It is effective in settings that are non-trivial to incorporate into existing algorithms, including cases with pointwise costs, heteroscedastic noise, and multi-fidelity setting. Our main result is a general regret guarantee that covers these aspects. Next, we consider GP optimization with robustness requirement: An adversary may perturb the returned design, and so we seek to find a robust maximizer in the case this occurs. This requirement is motivated by, e.g., settings where the functions during optimization and implementation stages are different. We propose a novel robust confidence-bound based algorithm. The rigorous regret guarantees for this algorithm are established and complemented with an algorithm-independent lower bound. We experimentally demonstrate that our robust approach consistently succeeds in finding a robust maximizer while standard BO methods fail. We then investigate the problem of GP optimization in which the reward function varies with time. The setting is motivated by many practical applications in which the function to be optimized is not static. We model the unknown reward function via a GP whose evolution obeys a simple Markov model. Two confidence-bound based algorithms with the ability to "forget" about old data are proposed. We obtain regret bounds for these algorithms that jointly depend on the time horizon and the rate at which the function varies. Finally, we consider the maximization of a set function subject to a cardinality constraint $k$ in the case a number of items $\tau$ from the returned set may be removed. One notable application is in batch BO where we need to select experiments to run, but some of them can fail. Our focus is on the worst-case adversarial setting, and we consider both \emph{submodular} (i.e., satisfies a natural notion of diminishing returns) and \emph{non-submodular} objectives. We propose robust algorithms that achieve constant-factor approximation guarantees. In the submodular case, the result on the maximum number of allowed removals is improved to $\tau = o(k)$ in comparison to the previously known $\tau=o(\sqrt{k})$. In the non-submodular case, we obtain new guarantees in the support selection and batch BO tasks. We empirically demonstrate the robust performance of our algorithms in these, as well as, in data summarization and influence maximization tasks.