Mass spectrometry (MS) is generally viewed as a highly complex and demanding technique, full of difficulties and apprehensions. Ease and simplicity have been infrequently used descriptors of MS but a series of revolutionary developments is turning a complex technique into a model of simplicity, making MS easier than ever. Focusing on spray-based ambient desorption/ionization techniques, we discuss how previously unthinkable goals for MS - (1) to bring it to a real world open atmosphere environment; (2) to perform fast, selective, and highly sensitive chemical and biochemical MS analysis with ease while (3) avoiding pre-separation and sample work-up for samples in their natural environment and therefore, at the end, (4) to make MS accessible in wherever MS is needed and by whoever needs it - have become feasible. Without compromising the unique combination of high speed, selectivity, sensitivity and separation competences, simplicity has become a new MS attribute - a fifth 'S' in the unique 5 S set of MS trademark features.