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Sampling is a key issue for answering most ecological and evolutionary questions. The importance of developing a rigorous sampling design tailored to specific questions has already been discussed in the ecological and sampling literature and has provided useful tools and recommendations to sample and analyse ecological data. However, sampling issues are often difficult to overcome in ecological studies due to apparent inconsistencies between theory and practice, often leading to the implementation of simplified sampling designs that suffer from unknown biases. Moreover, we believe that classical sampling principles which are based on estimation of means and variances are insufficient to fully address many ecological questions that rely on estimating relationships between a response and a set of predictor variables over time and space. Our objective is thus to highlight the importance of selecting an appropriate sampling space and an appropriate sampling design. We also emphasize the importance of using prior knowledge of the study system to estimate models or complex parameters and thus better understand ecological patterns and processes generating these patterns. Using a semi-virtual simulation study as an illustration we reveal how the selection of the space (e.g. geographic, climatic), in which the sampling is designed, influences the patterns that can be ultimately detected. We also demonstrate the inefficiency of common sampling designs to reveal response curves between ecological variables and climatic gradients. Further, we show that response-surface methodology, which has rarely been used in ecology, is much more efficient than more traditional methods. Finally, we discuss the use of prior knowledge, simulation studies and model-based designs in defining appropriate sampling designs. We conclude by a call for development of methods to unbiasedly estimate nonlinear ecologically relevant parameters, in order to make inferences while fulfilling requirements of both sampling theory and field work logistics.