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In online marketing, the advertisers' goal is usually a tradeoff between achieving high volumes and high profitability. The companies' business units customarily address this tradeoff by maximizing the volumes while guaranteeing a lower bound to the Return On Investment (ROI). This paper investigates combinatorial bandit algorithms for the bid optimization of advertising campaigns subject to uncertain budget and ROI constraints. We study the nature of both the optimization and learning problems. In particular, when focusing on the optimization problem without uncertainty, we show that it is inapproximable within any factor unless P=NP, and we provide a pseudo-polynomial-time algorithm that achieves an optimal solution. When considering uncertainty, we prove that no online learning algorithm can violate the (ROI or budget) constraints during the learning process a sublinear number of times while guaranteeing a sublinear pseudo-regret. Thus, we provide an algorithm, namely GCB, guaranteeing sublinear regret at the cost of a potentially linear number of constraints violations. We also design its safe version, namely GCB_{safe}, guaranteeing w.h.p. a constant upper bound on the number of constraints violations at the cost of a linear pseudo-regret. More interestingly, we provide an algorithm, namely GCB_{safe}(ψ,ϕ), guaranteeing both sublinear pseudo-regret and safety w.h.p. at the cost of accepting tolerances ψand ϕin the satisfaction of the ROI and budget constraints, respectively. This algorithm actually mitigates the risks due to the constraints violations without precluding the convergence to the optimal solution. Finally, we experimentally compare our algorithms in terms of pseudo-regret/constraint-violation tradeoff in settings generated from real-world data, showing the importance of adopting safety constraints in practice and the effectiveness of our algorithms.