In an acid-base reaction the reactant where the bond to H is breaking is the acid and the reactant where the bond to H is forming is the base. Likewise, the product formed when the bond to H is broken is called the conjugate base and the product formed when the bond to H is formed is called the conjugate acid. For any group of acids, H-X (where X can be almost any other atom), the strongest acid will have the most stable conjugate base. Since stability is inversely correlated with basicity, it is possible to express the same idea by saying: the stronger the acid, the weaker the conjugate base. The converse is also true the weaker the acid, the stronger the conjugate base.  It is important to make the distinction that not all weak acids are strong bases.  Methane (CH₄) is a weak acid, but it cannot serve as a base as it does not have a lone pair. A better way to make the distinction is weak acids have strong conjugate bases where the conjugate base of CH₄, CH₃^– is an extremely strong base.

While charged species are more unstable than neutral species, an acid is becoming more negative with the loss of a proton so the stability of the new lone pair on the conjugate base is significant in determining how favorable the reaction will be. Generally, the lower the charge density, the more stable a species is. In the same way, high charge densities tend to be less stable than low charge densities. In order to spread out a charge to gain greater stability the more volume/surface area a charge occupies the more stable it will be. So as we go down the periodic table from Fluoride to Iodide anions, the magnitude of the negative charge does not change, but the volume that it occupies does. Iodide ion, being considerably larger than fluoride ion (206 pm vs. 119 pm) is more stable, which means that H-I is a stronger acid than H-F. In addition, adding electron withdrawing groups to an atom can have a similar effect to that of increasing electronegativity. For example, replacing a hydrogen with a chloride stabilizes the negative charge increases.

Resonance is yet another way a negative charge can be dispersed in a molecule. If the conjugate base has a charge which can interact with adjacent double bonds or p orbitals, the stability of the conjugate base will increase. This leads to increased acidity of what becomes the conjugate acid. The closer a negative charge is to the nucleus, the more stable it is. Another way of saying this is when considering sp3 (alkane) to sp2 (alkene) to sp (alkyne) hybridization, the stability of the negative charge increases. Thus, alkynes are remarkably acidic compared to alkanes.

The equilibrium constant Ka, also known as the acidity constant is a measure of how likely an acid is to give up a proton or an H. By taking the logarithm of the acidity constant Ka, multiply it by negative, we obtain the pka. The most common measure of how acidic a substance is. The smaller the pka (as well as the larger and more negative), the stronger or more likely to give up a proton the acid is. If the pH is below the pka, the proton remains on the molecule. If the pH rises above the pka, then the proton ionizes or is removed from the molecule. If the pH equals the pka then according to Henderson Hasselbalch there is 50% of the protonated acid and 50% of the deprotonated conjugate base.